9cz2 | pdb_00009cz2
Cryo-EM structure of a nautilus-like HflK/C assembly in complex with FtsH AAA protease
Structural highlights
FunctionHFLK_ECOLI HflC and HflK help govern the stability of phage lambda cII protein, and thereby control the lysogenization frequency of phage lambda. HflKC inhibits the SecY-degrading activity of FtsH, possibly helping quality control of integral membrane proteins.[1] Publication Abstract from PubMedThe AAA protease FtsH associates with HflK/C subunits to form a megadalton-size complex that spans the inner membrane and extends into the periplasm of E. coli. How this bacterial complex and homologous assemblies in eukaryotic organelles recruit, extract, and degrade membrane-embedded substrates is unclear. Following the overproduction of protein components, recent cryo-EM structures showed symmetric HflK/C cages surrounding FtsH in a manner proposed to inhibit the degradation of membrane-embedded substrates. Here, we present structures of native protein complexes, in which HflK/C instead forms an asymmetric nautilus-shaped assembly with an entryway for membrane-embedded substrates to reach and be engaged by FtsH. Consistent with this nautilus-like structure, proteomic assays suggest that HflK/C enhances FtsH degradation of certain membrane-embedded substrates. Membrane curvature in our FtsH*HflK/C complexes is opposite that of surrounding membrane regions, a property that correlates with lipid scramblase activity and possibly with FtsH's function in the degradation of membrane-embedded proteins. An asymmetric nautilus-like HflK/C assembly controls FtsH proteolysis of membrane proteins.,Ghanbarpour A, Telusma B, Powell BM, Zhang JJ, Bolstad I, Vargas C, Keller S, Baker TA, Sauer RT, Davis JH EMBO J. 2025 May;44(9):2501-2513. doi: 10.1038/s44318-025-00408-1. Epub 2025 Mar , 13. PMID:40082723[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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